Abstract

A recently introduced computational algorithm to extend time scales of atomically detailed simulations is illustrated. The algorithm, milestoning, is based on partitioning the dynamics to a sequence of trajectories between “milestones” and constructing a non-Markovian model for the motion along a reaction coordinate. The kinetics of a conformational transition in a blocked alanine is computed and shown to be accurate, more efficient than straightforward molecular dynamics by a factor of about 9, and nonexponential. A general scaling argument predicts a linear speedup with the number of milestones for diffusive processes and an exponential speedup for transitions over barriers. The algorithm is also trivial to parallelize. As a side result, milestoning also produces the free energy profile along the reaction coordinate and is able to describe nonequilibrium motions along one (or a few) degrees of freedom.

Received 21 August 2006Accepted 20 February 2007Published online 10 April 2007

Acknowledgments:

The authors thank Eric van den Eijnden for many useful discussions, and John Straub and Eric Darve for pointing us to important references. This research was supported by a NIH Grant No. GM59796 to one of the authors (R.E.). The authors acknowledge NIH Grant No. RR020889 for the purchase of a computer cluster on which these calculations were performed.